This application proposes studies in a variety of areas relating to the chemistry and biology of human lymphocytes. The problems being studied involve the molecular basis of immune recognition, including the recognition of tumor cells, as well as factors which govern and regulate proliferation of human lymphocytes. The techniques being employed include protein chemistry and crystallography, molecular genetics, cellular immunology and virology. Specific areas of investigation are: 1) protein chemistry and crystallography of and the relationship of structure to function in class I MHC molecules and their bound peptides, 2) similar studies of class II MHC molecules, 3) the interaction of CD4 with the class Il MHC molecule through its D3 and D4 domains and with the protein tyrosine kinase p56(lck) through its intracytoplasmic region, 5) protein chemistry of T cell receptors and the mechanisms of development of T cells, 6) the role of HLA-C in NK allorecognition and other studies of NK cells, 7) the mechanism of transformation of B and T cells by Epstein Barr Virus, and 8) the regulation of expression and function of tumor necrosis factor alpha. They relate to tumor immunology and tumor cell proliferation in a variety of ways.